A CONSCIOUS SEPTIC DOG-MODEL WITH HEMODYNAMIC AND METABOLIC RESPONSES SIMILAR TO RESPONSES OF HUMANS

Abstract

A conscious septic dog model suitable for in vivo tracer studies was developed. Dogs weighing 10-20 kg underwent general anesthesia followed by the insertion of long-tern arterial, venous and portal cannulas and the formation of a long-term tracheostomy. After 7-10 days of convalescence, the animals were fed in the morning and 4 h later 1010 live Escherichia coli organisms were infused intra-arterially over .apprx. 30 min. One hour later a 2nd dose of 5 .times. 109 bacteria was given, again over 30 min. Resuscitation was provided by infusion of 1000 ml of lactated Ringer solution over 3 h. Twenty-four hours after the induction of sepsis the animals were hemodynamically stable and suitable for study. Cardiac output was increased from the control value of 185 .+-. 35 ml/kg .cntdot. min to 308 .+-. 44 ml/kg .cntdot. min in the septic animals. Heart rate was increased from 98 .+-. 10 to 125 .+-. 5 beats/min; arterial pressure was not significantly altered. Indirect calorimetry and primed constant infusions of radioactive and stable isotopes were used to assess a variety of metabolic parameters. The metabolic rate was increased .apprx. 25%; the energy for this increase was primarily provided by the increased oxidation of free fatty acids and triglyceride. The release of free fatty acids was .apprx. 3 times greater than the control value; triglyceride synthesis increased 500%. The oxidation rate of free fatty acids and the fatty acids contained in very low density lipoproteins-triglyceride increased 40% and 900%, respectively. Glucose production was maintained at approximately the control value; the rate of glucose oxidation (as measured with 14C) was also not significantly altered. The plasma insulin concentration was moderately elevated; plasma glucagon concentration was 5-6 times greater than the control value. Plasma catecholamine levels were increased significantly. This model is suitable for the performance of metabolic studies in sepsis. The induction of a hyperdynamic septic state in < 24 h avoids the complications of starvation and dehydration frequently seen in the various peritonitis and abscess models. The model is predictable in its time course and reproducibly creates a situation that hormonally, hemodynamically and metabolically resembles what is commonly seen in humans with sepsis.